Montpeilier Cedex 5, F raneeThe synthesis of rneso-2',3'-dideoxy-3'P-hydroxymethyl carbocyclic nucleosides as potential antiviral drugs via the alkylation of protected purines and pyrimidines with meso-P,P'-disubstituted cyclopentanols under Mitsunobu conditions is described. Chemical evidence for an unusual competitive 2-0-vs. N'-alkylation of 3-substituted pyrimidines is presented. p Series J. CHEM. SOC. PERKIN TRANS. I 1994 a Series 14a li 1 ii 'H HO B Yield(%) 6p Ura23 7P CytO(b) Sp A h 7 1 lop Gua56 B Yield(%) llp 2-O-Ura 46 12p 2-O-Thy 68 lap 2-0-Cyt 61 I ii 1 B Yield(%) B Yield(%) lla 2-0-UraO 6a Ura20 12a 2 -0 -Thy 0 7a Thy25 Qa Ade61 loOr Gua35 8a CYt(6, c ) dScheme 1 BR = disubstituted purine or pyrimidine with a C-N9 or C-N' link; B'R = disubstituted pyrimidine with a C-O2 link; i: Protected nucleobase (HBR or HB'R) (2 mol equiv.), alcohol (1 rnol equiv.), triphenylphosphine (3 mol equiv.), diethyl azodicarboxylate (DEAD) (3 rnol equiv.), THF-benzene (2 : 1 v/v), 0 "C, 12 h; ii: methanolic ammonia for adenine derivative in p series followed by HCl(IO%) in u series; HCI (10%) in water-1 ,4-dioxane (1 : 1 v/v) for guanine derivative in u series followed by NaOH (0.1 rnol dm-3) (4.4 mol equiv.) in water-1 ,Cdioxane (1 : 1 v/v) in both a and p series; MeONa-methanol for pyrimidine derivatives in both a and p series preceded by HCl (10%) in a series. a Compound obtained at lower temperature (see Table 1). The cytosine-containing carbocyclic nucleosides (C-N' link) were synthesized according to Scheme 3 from uracil precursors. Reaction not performed. No isolation of condensation products from purines and very low yields from thymine and uracil derivatives after deprotection step (see Table 1). Me02C 16p X = OH, Y = H l8p X = OTBDPS, Y = H (79%) 18a X = H, Y = OTBDPS (89%) L, 17 X = H, Y = OPNB (77%) ji 1 lea X = H, Y = OH (quant.) 20p X = OTBDPS, Y = H (80%) 1Sp X = OTBDPS, Y = H (75%) 20a X = H, Y = OTBDPS (quant.) 1901 X = H, Y = OTBDPS (quant.) I vi + vii 14p X = OH, Y = H (80%) vi L, 218 X = OTBDPS, Y = H (98%) 14a X = H, Y = OH (quant.) 150 X = OH, Y = H (quant.) Paper 4/007991